This P20 application proposes the creation of the Case Proteomics Center in HIV/AIDS &Drug Abuse, which is designed to apply state-of-the art proteomics and systems biology tools to investigate HIV pathogenesis in the context of drug abuse and provide significant biomarkers of HIV infection, co-infection with other viruses, and drug abuse. During the pilot phase, we will undertake three inter-related projects designed to provide a better understanding of the impact on immune function and activity in HIV-infected individuals who are also exposed to addictive drugs, and the important viral co-factor Hepatitis C (HCV). In each of these projects there will be a direct examination of the proteomic responses in epithelial or T-cells and parallel examination of plasma readouts from affected patients. A major outcome of these projects will be development of informative biomarkers and methods that can be used in large-scale population studies to further evaluate the impact of drug use on HIV disease. The Center will be directed by Dr Mark Chance, Director of the Case Center for Proteomics, and an internationally recognized expert in proteomics and system biology in collaboration with Dr Jonathan Karn, Chair of the Department of Molecular Biology &Microbiology and Co-Director of the Case Center for AIDS Research (CFAR), and an expert in HIV/AIDS molecular biology. The pilot projects are the work of a strong pre-existing multi-disciplinary team at Case that combines significant biological expertise in HIV/AIDS within the Department of Medicine, the Department of Molecular Biology &Microbiology, the Department of Biological Sciences (Dental School) and CFAR. These investigators have already assembled significant molecular biology and proteomics data to provide testable hypotheses within the context of three Pilot Projects served by a Proteomics and Bioinformatics Core. The three projects, with the cooperation of the clinical core of the Case CFAR, will recruit appropriate patient cohorts to provide relevant samples. The proteomics team in the Core will then conduct proteome expression analysis of cases versus relevant control populations, with statistically significant targets provided to the Bioinformatics team. This team will not only provide network analysis and pathway identification within the context of the biological questions to be addressed, but will correlate the proteomics pathway models with known pathways of drug addiction and HIV pathogenesis and will infer novel sub-networks by combined analysis of proteomics and microarray data.